Mammalian L1 elements (LINE-1) replicate by copying their RNA transcripts into DNA which is then integrated into the genome. In the last 15 million years this process has generated ~550,000 kb of L1 DNA in murine genomes, ~ 20% of the total. In humans L1 retrotransposition causes up to 0.2% of the genetic defects. The ~7 kb L1 element has four regions: a 5 untranslated region, (UTR); two open reading frames (ORFs I and II); a 3 UTR. The 5 UTR has a regulatory function, the ORF I protein binds RNA, the ORF II protein is a reverse transcriptase and endonuclease, and the 3 UTR forms complex intrastrand DNA and RNA structures. We, and others, have determined the evolutionary dynamics of rodent L1 elements and showed that they evolve rapidly with novel families continually replacing older ones. Since the products of past L1 families are retained, modern genomes contain both past and present replicatively successful L1 subfamilies. The subfamily structure of L1 DNA permits a comparative approach to the functional analysis of the L1 genome and for determining the natural history of L1 elements. Understanding the natural history of L1 elements is necessary for addressing several issues such as how novel L1 families arise, and the impact of L1 elements on their hosts. Accordingly, we have been examining the evolutionary dynamics of L1 elements in primates, including humans, which surprisingly had not yet been examined. We focused on the so called Ta family since the two putatively active human L1 elements so far identified are members of this family. We made the following findings: The Ta family consists of at least two subfamilies, Ta-0 and Ta-1. The Ta-0 family arose about 5 million years ago (Mya) and reached peak amplification 1-2 Mya. Ta-1 appeared ~3 Mya and it is seemingly replacing Ta-0 for replicative supremacy, although the Ta-0 subfamily still retains some activity. In agreement with the relative ages of these subfamilies, 47% of Ta-0 inserts are fixed in world wide human populations (8 of 17 loci), but only 23% (7 of 30 loci) of Ta-1 inserts are fixed. The Ta family is present only in humans and now contains about 700 members per haploid genome, 300 of which belong to the Ta-1 subfamily. Ta-1 elements have been accumulating at the same rate per generation as recently evolved rodent L1 families. Despite its prominence and recent activity, the Ta-1 subfamily was missed in a previous study aimed at identifying full length human L1 elements. Therefore, the previous results seriously under estimated both the number of potentially active human L1 elements and their genetic impact. The revelation of the Ta-1 subfamily by our phylogenetic analysis again vindicates this approach for investigating L1 biology. Given the importance of genetic polymorphisms for genetic mapping and population genetics we developed a method to isolate and characterize all of the L1 related polymorphisms in several human populations. We also hope to use these results to develop an assay for the L1 transposition rate (as opposed to the accumulation rate). We have just about completed the first phase of this work, namely the isolation of every member of the Ta-1 family. In addition, to providing the ground work for isolating polymorphic loci in other human populations, knowing the genetic environment of an entire L1 family may prove useful in identifying those factors responsible for its replicative success. And finally, we are also analyzing the evolutionary dynamics of L1 in other hominids, and have sequenced ~600 bp of a large number of L1 elements from chimpanzee, gorilla, and orangutan. In addition we are comparing sequence divergence between homologous sites of L1 insertion in these animals and humans in order to obtain a robust value the for the hominid molecular clock. This value will be not only useful for our studies but also to others on the comparative genomics of these species. - retrotransposons genetics polymorphism evolution L1 genomics mammals primates DNA phylogenetics